Our studies of host genes which influence hematopoietic system diseases associated with MuLV infection have been directed toward genetic factors controlling infection and disease induction by the B-tropic MuLV complex known as LP-BM5. Mouse strains most susceptible to the immunodeficiency disease (mouse AIDS or "MAIDS") induced by LP-BM5 are, as would be predicted, of the Fv-1b genotype, a background permissive to infection by and spread of B- tropic MuLVs. Only certain Fv-lb strains, however, were found to be sensitive: C57BL and I/St are highly susceptible while other Fv-1b strains such as BALB/c and A are resistant. Based on tests of selected inbred, recombinant inbred, and H-2 congenic mouse strains, we have determined that the major determinant of sensitivity lies within the MHC region. Haplotypes b, r, and j confer sensitivity, H-2k strains show partial sensitivity, while H-2d and H-2a strains are resistant. In crosses between C57BL (H- 2b) and H-2d or H-2a stains, sensitivity appears to be dominant. Further, tests of H-2 congenic and recombinant mice suggest that the major controlling element lies at the D end of H-2. In addition, it appears that certain combinations of H-2 gene elements, or genes outside the H-2 region, can affect the disease phenotype, e.g., the degree or rate of progression. Induction of disease is strongly correlated with replication of both the ecotropic and MCF components of the LP-BM5 mixture.